Do Atypical Antipsychotics Cause Stroke?
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Post hoc analyses of pooled results from 11 randomised controlled trials of risperidone and olanzapine in elderly dementia subjects revealed an increased incidence of cerebrovascular adverse events compared with placebo. Reanalysis of the risperidone trials suggests that some of the increased incidence may be accounted for by nonspecific events that were not strokes. Large observational administrative health database studies appear to confirm that risperidone and olanzapine are not associated with an increased risk of stroke in elderly patients compared with typical antipsychotics or untreated dementia patients. A larger number of subjects with vascular and mixed dementias were included in the risperidone studies compared with the olanzapine studies, which likely accounts for the increased incidence of cerebrovascular adverse events in the risperidone trials compared with the olanzapine studies. Potential mechanisms proposed to explain an association between atypical antipsychotics and cerebrovascular adverse events include thromboembolic effects, cardiovascular effects (e.g. orthostatic hypotension, arrhythmias), excessive sedation resulting in dehydration and haemoconcentration, and hyperprolactinaemia. However, there is little evidence to support these hypothesised mechanisms at present. The association between atypical antipsychotics and cerebrovascular adverse events requires further clarification. At the present time, this association is another factor that clinicians should consider when weighing the risks and benefits of treating behavioural and psychological disturbances in elderly dementia patients.
KeywordsRisperidone Olanzapine Atypical Antipsychotic Typical Antipsychotic Stroke Risk Factor
No pharmaceutical company support was received for this paper. Drs Herrmann and Lanctôt have previously received research support and speakers’ honoraria from Janssen Ortho Inc., Eli Lilly, Novartis, Pfizer, AstraZeneca, all manufacturers of atypical antipsychotics. The authors wish to acknowledge Dr Andrew Greenspan of Janssen Medical Affairs, LLC for providing data on file for risperidone, and Dr Jamie Karagianis of Eli Lilly Canada for providing data on file for olanzapine.
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